Dr Jessica Xu1, Dr Jieqing Jessica Xu1, Jeremiah Tan1, Dr Neda Amiri-Bostan-Abad1,3, Dr Monica Beaulieu1, Dr Jessica Liauw2, Dr Wee-Shian Chan1, Dr Tessa Chaworth-Musters1
1Department of Medicine, University of British Columbia, Vancouver, Canada, 2Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada, 3Arthritis Research Canada, Vancouver, Canada
Biography:
Biographies to come
Abstract:
Intrahepatic cholestasis of pregnancy (IHCP) is associated with significant maternal morbidity and fetal mortality. Uncommon presentations such as early gestational age onset, severely elevated bile acids, or treatment refractoriness, require further investigation.
We present a 31-year-old primiparous patient with systemic lupus erythematosus (SLE) and lupus nephritis who developed generalized pruritus and new hypertension at 29 weeks’ gestation. Her SLE was quiescent before and throughout pregnancy; she was managed with azathioprine, hydroxychloroquine, and tacrolimus. Workup demonstrated severely elevated bile acids (234umol/L) and mildly elevated ALT (60U/L) and bilirubin (28umol/L) levels. There was no evidence of SLE flare based on symptoms and serology. She was admitted with a diagnosis of IHCP and gestational hypertension, and was started on ursodiol (500 mg BID) and hydroxyzine (10 mg TID). Two days after treatment initiation, she continued to have severe pruritus. Literature review revealed that azathioprine could be a contributor to cholestasis. Azathioprine was discontinued 3 days after admission, and 6-Methylmercaptopurine levels (an azathioprine metabolite) were twice the upper limit of normal, indicating potential supratherapeutic levels. Within days of discontinuation, bile acid levels and pruritus improved, with subsequent normalization over 2 weeks. Ursodiol and hydroxyzine were discontinued, and she remained asymptomatic for the remainder of pregnancy. She delivered via Cesarean section at 36 weeks because of preeclampsia. Azathioprine was restarted at a low dose postpartum and was well tolerated.
The diagnosis of IHCP in pregnancy is made after the exclusion of other potential causes of cholestasis. In our case, azathioprine, a commonly used immunosuppressant, has been associated with intrahepatic cholestasis. Key elements seen in this specific situation are high bile acids, minimal to absent elevation of liver enzymes, early presentation, and refractoriness to ursodiol. This case highlights the importance of medication review, and assessment for possible secondary contributors to the development of cholestasis during pregnancy.
Keywords
Intrahepatic cholestasis of pregnancy, IHCP, azathioprine induced cholestasis
References
1. Céruti H, Kayem G, Guilbaud L, Dussaux C, Gervais A, Beaufrère A, Coffin B, Mandelbrot L, Maisonneuve E. Intrahepatic cholestasis of pregnancy associated with azathioprine: a case series. Journal of Gynecology Obstetrics and Human Reproduction. 2021 Apr 1;50(4):102083.
2. Wolf MF, Sloma R, Akria L, Rimon E, Wiener Y, Haggai MC, Lowenstein L. Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature. Taiwanese Journal of Obstetrics and Gynecology. 2023 Sep 1;62(5):761-4.
3. Selinger CP, Rosiou K, Broglio G, Lever G, Chiu CM, Stocker LJ, Chipeta H, Glanville T. Antenatal thiopurine exposure in women with IBD is associated with intrahepatic cholestasis of pregnancy. Expert Opinion on Drug Safety. 2023 Nov 2;22(11):1091-7.